VOLUME 23 䡠 NUMBER 30 䡠 OCTOBER 20 2005

JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T

Quality of Life and Sexual Functioning in Cervical

Cancer Survivors
Michael Frumovitz, Charlotte C. Sun, Leslie R. Schover, Mark F. Munsell, Anuja Jhingran,
J. Taylor Wharton, Patricia Eifel, Therese B. Bevers, Charles F. Levenback, David M. Gershenson,
and Diane C. Bodurka
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From the Departments of Gynecologic

Oncology, Behavioral Science, Biostatis- A B S T R A C T
tics and Applied Mathematics, Radia-
Copyright © 2024 American Society of Clinical Oncology. All rights reserved.

tion Oncology, and Clinical Cancer Purpose

Prevention, The University of Texas
M.D. Anderson Cancer Center,
Houston, TX.
Submitted November 6, 2004; accepted
June 29, 2005.
Supported by the Deferred Tuition Fund
grant from The University of Texas at
Houston School of Public Health.
Presented at the 35th Annual Meeting of
the Society of Gynecologic Oncologists,
San Diego, CA, February 7-11, 2004.
Authors’ disclosures of potential con-
flicts of interest are found at the end of
this article.
Address reprint requests to Michael
Frumovitz, MD, MPII, Department of
Gynecologic Oncology, 1155 Herman
Pressler, CPB6.3244, Unit 1362,
Houston, TX 77030; e-mail: mfrumovitz@
mdanderson.org.
© 2005 by American Society of Clinical
Oncology
0732-183X/05/2330-7428/$20.00
To compare quality of life and sexual functioning in cervical cancer survivors treated with
either radical hysterectomy and lymph node dissection or radiotherapy.
Methods
Women were interviewed at least 5 years after initial treatment for cervical cancer. Eligible
women had squamous cell tumors smaller than 6 cm at diagnosis, were currently disease-free,
and had either undergone surgery or radiotherapy, but not both. The two treatment groups were
then compared using univariate analysis and multivariate linear regression with a control group of
age- and race-matched women with no history of cancer.
Results
One hundred fourteen patients (37 surgery, 37 radiotherapy, 40 controls) were included for
analysis. When compared with surgery patients and controls using univariate analysis,
radiation patients had significantly poorer scores on standardized questionnaires measuring
health-related quality of life (physical and mental health), psychosocial distress and sexual
functioning. The disparity in sexual function remained significant in a multivariate analysis.
Univariate and multivariate analyses did not show significant differences between radical
hysterectomy patients and controls on any of the outcome measures.
Conclusion
Cervical cancer survivors treated with radiotherapy had worse sexual functioning than did
those treated with radical hysterectomy and lymph node dissection. In contrast, these data
suggest that cervical cancer survivors treated with surgery alone can expect overall quality
of life and sexual function not unlike that of peers without a history of cancer.

DOI: 10.1200/JCO.2004.00.3996 J Clin Oncol 23:7428-7436. © 2005 by American Society of Clinical Oncology

modality involves distinct clinical acute and

INTRODUCTION
Papanicolaou smear screening has led to a
decrease in the incidence of cervical cancer
with 10,370 new cases diagnosed and 3,710
attributable deaths in 2005 in the United
States.1 Additionally, over half of women
are diagnosed with stage I disease when the
tumor is clinically limited to the cervix.2
Primary treatment with surgery or irradia-
tion alone cures 85% to 90% of patients
with stage I cervical cancer.3-6 Despite simi-
lar effectiveness, however, each treatment
late complications.
The surgical approach to early-stage cer-
vical cancer consists of radical hysterectomy
and bilateral lymph node dissection, with or
without accompanying oophorectomy or
ovarian transposition. Blood loss remains the
most significant intraoperative complication
with transfusion rates reaching as high as
80%.7,8 Postoperatively, patients may experi-
ence febrile morbidity, deep vein thrombosis,
pulmonary embolism, wound dehiscence,
postoperative bladder dysfunction, and

7428
 QOL in Cervical Cancer
fistula formation. In addition, a small but real risk of operative
mortality exists with the surgery. Long-term complications can
include bladder hypotonia requiring chronic self-catheterization,
ureteral strictures, and chronic leg lymphedema.9,10
Radiotherapy, typically consisting of external beam ra-
diation followed by intracavitary radiation, has its own
spectrum of complications. Potential complications from
intracavitary radiation include uterine perforation and fe-
brile morbidity. Although deep vein thrombosis, pulmo-
nary embolism, and even death are potential risks with
intracavitary radiotherapy, they are exceedingly rare.11 Pa-
tients who receive radiation may also experience early small
bowel complications (obstruction); early or late large bowel
complications (bleeding, stricture, fistulae, perforation);
late urinary complications (hematuria, ureteral stenosis,
vesicovaginal fistula); and vaginal atrophy, shortening, or
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agglutination.12 The latter can make sexual intercourse dif-
ficult or even impossible. Although radical hysterectomy
Copyright © 2024 American Society of Clinical Oncology. All rights reserved.
and radiotherapy are associated with comparable rates of
complications, the quality, chronicity, and severity of these
complications are difficult to compare.13,14
Whether the patient undergoes primary surgery or ra-
diotherapy depends on a variety of factors, including tumor
characteristics, comorbid medical conditions, and patient
and provider preference. Patients who are likely to require
adjuvant radiotherapy following radical hysterectomy often
undergo primary radiotherapy in an effort to minimize the
morbidity and mortality associated with combined treatment
modalities. Factors that might dispose physicians to recom-
mend primary radiotherapy include large tumor volume, lym-
phatic involvement, aggressive tumor histology, and depth of
invasion.14 In reality, however, many women with stage IB1
tumors are equally good candidates for either surgical manage-
ment or radiotherapy. In these situations, the clinical decision
is often based on patient or provider preference.
The objective of this study was to perform a compari-
son of the quality of life (QOL) of women with early-stage
cervical cancer that could be treated equally effectively with
either surgery or radiotherapy. Standardized questionnaires
were used to measure outcomes, and a group of healthy age-
and race-matched women with no personal history of can-
cer was included in the comparison to determine if any
differences in QOL exist between women with cervical can-
cer and women without a history of cancer. The ultimate
aim of the study was to provide patients and providers with
additional empirical information to help guide their treat-
ment choice.
METHODS
Study Population
The protocol was approved by the institutional review board
at The University of Texas M.D. Anderson Cancer Center.
Women with cervical cancer treated at M.D. Anderson from 1991
www.jco.org
to 1998 were identified through an institutional patient database.
Patients whose primary language was English or Spanish were
eligible if they were younger than 55 years at the time of treatment;
had undergone treatment at least 5 years previously; had squa-
mous cell, adenocarcinoma, or adenosquamous histologies; and
had lesions smaller than 6 cm in diameter confined to the cervix
(stage I). Although International Federation of Gynecology and
Obstetrics (FIGO) subdivides stage I disease into stages Ia1, Ia2,
Ib1, and Ib2, tumors ⱕ 6 cm confined to the cervix was chosen for
inclusion, as these lesions are thought to, clinically, behave simi-
larly. Patients were excluded if they received a combination of
surgical and radiation therapies, had concurrent chemoradiother-
apy therapy, developed recurrent disease, or were treated for other
malignancies (except for adequately treated basal cell or squamous
cell skin cancer). Radiation patients received a mean dose of 85.7
Gy to point A.
Age- and race-matched controls were recruited from the
M.D. Anderson Cancer Center Cancer Prevention Clinic. Ex-
clusion criteria were previous cancer diagnosis other than ade-
quately treated basal cell or squamous cell skin cancers and
previous hysterectomy.
Instruments
Health-related QOL was measured using the Short Form-12
(SF-12).15 This 12-item version of the widely used SF-36 question-
naire provides mental health (MCS) and physical health (PCS)
component summary scores that measure self-perceived health-
related QOL.
Emotional distress was assessed using the Brief Symptom
Index-18 (BSI-18).16 The BSI-18 yields three primary dimension
scores—somatization, depression, and anxiety—as well as a
Global Severity Index (GSI), which summarizes the overall level of
psychological distress.
Severity of menopausal symptoms was calculated with the
Menopausal Survey.17 The survey has seven questions that target
common physical and psychological symptoms of menopause.
Two instruments were used to examine how treatment af-
fected social relationships. The Abbreviated Dyadic Adjustment
Scale (A-DAS), a seven-question survey, was administered to
women who were married or who had been in a serious relation-
ship for at least 6 months.18 Participants who were single and not
in a serious relationship were asked the five-item dating subscale of
the Cancer Rehabilitation Evaluation System (CARES), which
measures comfort in dating.19 This subscale of the larger CARES
instrument has not been validated as a stand-alone survey.
Finally, the Female Sexual Function Index (FSFI), a 19-item
multiple-choice questionnaire, was administered. This survey mea-
sures five domains, including sexual desire, arousal (both subjective
and physiologic), lubrication, orgasm, satisfaction, and pain.20
For the SF-12 and FSFI surveys, multiple-choice items have
response formats that range, for example, from “never” to “al-
ways,” or “very low” to “very high.” The other four instruments
employ Likert-type numbered scales. Higher scores correlate with
better functioning on the SF-12, FSFI, A-DAS, and CARES instru-
ments while lower scores reflect better functioning on the BSI-18
and menopausal survey.
Demographic data, including age, race, level of education,
and medical comorbidities, were collected for all participants.
Radiation patients were assumed to be menopausal by virtue of
their treatment. Menopausal status of surgical patients was as-
sessed by review of ovarian procedures performed at time of
7429
 Frumovitz et al

radical hysterectomy. Controls were asked their perceived meno-
pausal status. Clinical stage, histology, tumor grade, depth of
invasion, and other pertinent characteristics were abstracted from
patient charts.
Administration
Letters of introduction were mailed to eligible patients and
controls describing the nature of the study and asking for the
woman’s participation. The letter also stated that a project inter-
viewer would telephone eligible women and specified that $15
would be given to all participants.
The same female bilingual (English and Spanish) interviewer
administered all the surveys. The interviewer was blinded to each
patient’s treatment history. Once women verbally agreed to par-
ticipate, they were read an informed consent statement that met
criteria defined by the Health Insurance Portability and Account-
ability Act (HIPAA), as well as by our institution. The survey took
an average of 32 minutes to administer (range, 15 to 60 minutes).
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have two separate primary cancers at time of surgery. The
remaining 74 patients were evenly distributed among the
two treatment modalities (n ⫽ 37 per group). Ninety-two
age- and race-matched women from our Cancer Prevention
Clinic were identified for participation. Of these, 23 could
not be reached due to incorrect or unattainable contact
information, 19 declined participation, and 10 were ex-
cluded because of prior hysterectomy. The final control
group consisted of 40 women who were interviewed for a
response rate of 43%.
Demographic and Medical Characteristics
Demographic and clinical characteristics of patients
and controls are presented in Table 1. No significant differ-
ences existed among the three groups with regard to current
age, body mass index, race, history of tobacco use, hyper-
tension/coronary artery disease, diabetes, hypothyroidism,

Statistical Analysis
The study was powered to detect a 15% relative difference on
Copyright © 2024 American Society of Clinical Oncology. All rights reserved.

the SF-12 between the two treatment groups and the control
group. The Bonferroni adjustment was used to control for multi- Table 1. Demographic and Clinical Characteristics of Study Participants
ple comparisons, and an ␣ level of .017 was considered significant. No. of Patients P
To achieve 80% power, we calculated that a sample size of 38 Rad All
women per group was necessary. Hyst Radiation Controls Patientsⴱ Three†
For comparisons between the treatment groups, t tests for
Total No. 37 37 40 NS NS
independent samples, Mann-Whitney U tests, and ␹2 tests were Mean age, years 43.6 46.9 42.8 NS NS
utilized. For univariate comparison of outcome measures between BMI, kg/m2 29.3 31.1 26.4 NS NS
the treatment groups with the control group, one-way ANOVA Race/ethnicity NS NS
and ␹2 analyses were conducted. Univariate analyses were adjusted White 28 23 26
for multiple comparisons using Tukey’s HSD (honestly significant Hispanic 7 4 6
difference) Test. Multivariate linear regression models were then Black 2 9 6
constructed. For the SF-12 PCS, SF-12 MCS, BSI-18 GSI, and FSFI Asian 0 1 2
overall scores, univariate analyses were performed for the follow- Marital status 0.04 .03
ing independent variables: age, marital status, religion, education, Married 33 26 36
body mass index, current smoking status, number of cigarette Single 4 11 4
packs smoked per year, medical comorbidities, menopausal symp- Education NS ⬍ .001
tom scores, and study group (radiation, surgery, and control). No HS 5 8 0
Backward elimination (P ⬍ .10 on univariate analysis to be con- HS diploma 11 14 7
sidered in model) was used to identify which independent vari- Some college 1 0 0
ables were associated with SF-12 PCS, SF-12 MCS, BSI-18 GSI, College degree 16 14 29
and FSFI overall scores when comparing the three arms. A similar Postgraduate 4 1 4
Smoking
analysis with the addition of stage, histology and tumor grade was
Ever smoked NS NS
also modeled to compare the radical hysterectomy and irradiated
Yes 9 13 9
patients. All data were analyzed using SPSS 11.5 for Windows
No 28 24 31
(SPSS Inc, Chicago, IL).
Pack years 4.3 10.8 2.7 NS .03
Comorbidities
HTN/CAD 0 4 6 NS NS
RESULTS Depression 4 0 8 NS .02
Diabetes 0 1 1 NS NS
Hypothyroid 0 2 2 NS NS
One hundred forty-five patients (90 treated with radical Asthma/COPD 0 1 2 NS NS
hysterectomy and 55 treated with radiotherapy) who met Other 1 1 2 NS NS
the inclusion criteria were identified. Sixty-seven were elim- Abbreviations: Rad Hyst, radical hysterectomy; HS, high school; HTN,
inated because they could not be contacted (n ⫽ 61) or hypertension; CAD, coronary artery disease; COPD, chronic obstructive
declined participation (n ⫽ 6). The remaining 78 were pulmonary disease.
ⴱ
Comparison of patients treated with radical hysterectomy versus pa-
interviewed for an overall response rate of 54%. Four were tients treated with radiation, using independent t test or Mann-Whitney.
excluded after data collection for the following reasons: two †Comparison of patients treated with radical hysterectomy versus
patients treated with radiation versus controls, using adjustments for
patients underwent both radiation and hysterectomy, one multiple comparisons.
patient exceeded the age limit, and one patient was found to

7430 JOURNAL OF CLINICAL ONCOLOGY

 QOL in Cervical Cancer

asthma/chronic obstructive pulmonary disease, or other

Table 3. Status of Ovaries in Radical Hysterectomy Patients (n ⫽ 37)
comorbidities (hepatitis [n ⫽ 1], migraines [n ⫽ 2], and
fibromyalgia [n ⫽ 1]). Although no differences existed Surgical Procedure No.

among the three groups in terms of ever having smoked, a None (ovaries intact) 11
Bilateral SO 10
significant difference did exist in the amount of tobacco
Unilateral SO 6
used, as defined by the packs per year with radiation pa- Bilateral transposition 5
tients reporting significantly greater tobacco use (P ⫽ .03) Unilateral SO/unilateral transposition 5
irradiated patients also reported less education than surgi- Abbreviation: SO, salpingoophorectomy.
cally treated patients and controls (P ⬍ .001). Women in
the control group had more clinical diagnoses of depression
than women in the treatment groups (P ⫽ .02).
Table 2 summarizes medical information for patients
in both treatment groups. Irradiated patients had a signifi- in the other two groups. Radiation patients reported signif-
cantly higher stage of disease than patients treated with icantly more anxiety than surgery patients but did not differ
surgery (P ⬍ .001). Surgical patients were more likely to significantly from controls. Radiation patients also had sig-
have adenocarcinoma or adenosquamous tumors than ir- nificantly higher scores on the GSI than did either surgery
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radiated patients (P ⫽ .033). No significant difference ex- patients or controls. No significant differences existed be-
isted between the groups in terms of time since diagnosis, tween surgery patients and controls on any of the three
Copyright © 2024 American Society of Clinical Oncology. All rights reserved.

tumor grade, or depth of invasion. Twenty-four controls BSI-18 subscales or on the GSI.
(60%) reported still having regular menstrual cycles; the
remaining 16 (40%) classified themselves as menopausal.
Ovarian procedures performed at the time of radical hyster-
Table 4. Univariate Analysis of Outcome Variables for Surgical Patients,
ectomy are detailed in Table 3. Radiation Patients, and Controls

QOL Outcomes Rad Hyst Radiation Controls

(n ⫽ 37) (n ⫽ 37) (n ⫽ 40) Pⴱ
Table 4 presents outcome scores for all six instruments.
Irradiated patients reported significantly worse health- SF-12
PCS 53.7 45.1 53.5 ⬍ .001
related QOL as measured by the physical health component
MCS 50.5 47.0 52.2 NS
of the SF-12. Mental component scale scores did not differ BSI-18†
significantly among the three groups. Somatization 46.5 52.7 43.4 .005
Depression 45.5 51.9 45.7 .01
Psychological Distress Anxiety 42.0 46.8c 42.5 .04
On the BSI-18, radiation patients reported significantly GSI 42.4 50.8 41.3 ⬍ .001
more somatization and depressive symptoms than women Menopause scale‡
Hot flashes 0.8 1.3 0.6 .04
Vaginal dryness 0.4 1.1 0.3 ⬍ .001
Urinary symptoms 0.6 1.2 0.5 .02
Table 2. Clinical Characteristics of Cervical Cancer Patients Treated
Total score 0.6 1.2b 0.4 ⬍ .001
With Radical Hysterectomy or Radiotherapy
A-DAS 26.3 22.7 23.9 NS
Rad Hyst Radiation CARES 1.3 1.7 1.0 NS
(n ⫽ 37) (n ⫽ 37) Pⴱ
FSFI
Years since diagnosis 7.5 7.0 NS Desire 3.4 2.9 3.6 NS
Stage, No. of patients ⬍ .001 Arousability 4.0 2.6 4.3 .006
Ia1 1 0 Lubrication 4.5 2.9 4.6 .003
Ia2 3 0 Orgasm 4.2 2.8 4.3 .02
Ib1 33 22 Satisfaction 4.4 3.2 4.7 .006
Ib2 0 15 Pain 4.6 2.7 5.0 ⬍ .001
Histology, No. of patients .033 Overall score 25.1 17.1 26.4 .001
Squamous 18 27
Abbreviations: Rad Hyst, radical hysterectomy; SF-12, Short Form-12; PCS,
Adenocarcinoma 15 10 Physical Component Score; MCS, Mental Component Score; BSI-18, Brief
Adenosquamous 4 0 Symptom Index-18; GSI, Global Severity Index; A-DAS, Abbreviated Dyadic
Grade, No. of patients NS Adjustment Scale; CARES, Cancer Rehabilitation Evaluation System; FSFI,
1 10 5 Female Sexual Functioning Index; NS, not significant.
ⴱ
P value represents difference in comparison of radiotherapy patients
2 10 12 versus controls and radical hysterectomy arms. The larger of the two
3 17 20 P values is reported. No significant difference existed in scores for radical
Depth of invasion, mm 3.6 4.0 NS hysterectomy patients and controls on any of the instruments utilized.
†Lower score correlates with better quality of life.
Abbreviation: Rad Hyst, radical hysterectomy. ‡Significantly lower (P ⬍ .05) when compared with radical hysterectomy,
ⴱ
Two-group analysis using independent t test or ␹2. but no significant difference (P ⫽ .06) when compared with controls.

www.jco.org 7431
 Frumovitz et al

Menopausal Symptoms committed relationships among the three groups on the

Radiation patients reported a significantly higher fre- A-DAS or CARES surveys.
quency of symptoms such as hot flashes, vaginal dryness,
Multivariate Analyses of Outcome Variables
and urinary complaints than did surgery patients and con-
Multivariate analyses were performed to assess the in-
trols. Overall menopausal symptoms were significantly more
dependent association of variables with four of the outcome
bothersome for women who had received radiotherapy. No
measures, the SF-12 PCS, the SF-12 MCS, the BSI-18 GSI,
difference in menopausal symptoms existed in the subscales
and overall sexual functioning on the FSFI (Table 5). Irra-
or overall scores between surgery patients and controls.
diated patients showed significantly worse sexual function-
Eleven (30%) of 37 surgical patients also underwent
ing as measured by the FSFI. Their self-perceived physical
concurrent bilateral salpingoophorectomy. When this
well-being was also worse than that of the others (P ⫽ .07).
group of patients made surgically menopausal was com-
Interestingly, menopausal symptoms had a significant neg-
pared with irradiated women, radiotherapy patients de-
ative association with all four outcome measures. Women
scribed significantly more menopausal symptoms.
who smoked reported poorer mental health and more emo-
Sexual Function and Relationship Satisfaction tional distress. Conversely, being married was related to
Scores on the FSFI did not reveal any difference in better physical health and sexual functioning.
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sexual desire as reported by the three groups. However, On multivariate analysis of the treatment groups, irra-
irradiated women had more difficulty becoming sexually diated patients had statistically significant worse sexual func-
Copyright © 2024 American Society of Clinical Oncology. All rights reserved.

aroused, attaining vaginal lubrication, reaching orgasm,
and achieving sexual satisfaction. Also, irradiated women
reported significantly more pain with intercourse than did
radical hysterectomy or control group women. The total
scores of irradiated patients revealed significantly worse
overall sexual functioning than did the scores of surgery
patients or controls. No statistical difference existed be-
tween the surgery patients or controls in any of the sexual
functioning subscales or the overall score. No statistically
significant difference existed in satisfaction with dating or
tioning as compared to surgical patients after accounting for
tumor size, histology, and grade (Table 6). The difference on
the SF-12 PCS scale again approached statistical significance in
this comparison (P ⫽ .07). Severity of menopausal symptoms
continued to be negatively associated with the SF-12 PCS and
MCS subscales. Finally, when limiting the comparison to only
those tumors less than 4 cm in size (stages IA1, IA2, and IB1),
irradiated patients had significantly worse sexual functioning
(P ⫽ .04) than surgery patients. There was no reported differ-
ence between the two groups in perceived physical functioning

Table 5. Multivariate Linear Regression Model Evaluating Independent Variables and Menopausal Symptom Scores for SF-12 PCS, SF-12 MCS,
BSI-18 GSI, and FSFI for All Three Groups
P
Independent Variable SF-12 PCS SF-12 MCS BSI-18 GSI FSFI Total

Age NS NS NS NS
Marital status .01 (⫹) NS NS ⬍ .001 (⫹)
Religion NS NS .02 (⫹) NS
Education NS NS NS NS
BMI NS NS S NS
Smoking, packs/yr NS .02 (⫺) .005 (⫺) NS
Current smoker NS NS NS NS
Hypertension/CAD NS NS .02 (⫺) NS
Depression NS NS NS NS
Diabetes NS NS NS NS
Thyroid disease NS NS NS NS
Asthma NS NS NS NS
Other comorbiditiesⴱ NS NS NS NS
Any comorbidity NS NS NS NS
Controls NS NS NS NS
Radiotherapy NS NS NS .03 (⫺)
Radical hysterectomy NS NS NS NS
Menopausal symptom score ⬍ .001 (⫺) .04 (⫺) .01 (⫺) .02 (⫺)

NOTE. P values are reported with either positive (⫹) or negative (⫺) association in parenthesis.
Abbreviations: SF-12 PCS, Short Form-12 Physical Component Score; SF-12 MCS, Short Form-12 Mental Component Score; BSI-18 GSI, Brief Symptom
Index-18 Global Severity Index; FSFI, Female Sexual Functioning Index; CAD, coronary artery disease.
ⴱ
Other comorbidities include hepatitis, migraines, and fibromyalgia.

7432 JOURNAL OF CLINICAL ONCOLOGY

 QOL in Cervical Cancer

Table 6. Multivariate Linear Regression Model Evaluating Independent Variables and Menopausal Symptom Score for SF-12 PCS, SF-12 MCS,
BSI-18 GSI, and FSFI Total for Radical Hysterectomy and Irradiated Patients
P
Independent Variable SF-12 PCS SF-12 MCS BSI-18 GSI FSFI Total

Age NS NS NS NS
Marital status NS NS NS ⬍ .001 (⫹)
Religion NS NS .001 (⫹) NS
Education NS NS NS NS
BMI NS NS NS NS
Smoking, packs/yr NS NS .002 (⫺) NS
Current smoker NS NS NS NS
Hypertension/CAD NS NS NS NS
Depression NS NS NS S
Diabetes NS NS NS NS
Thyroid disease NS NS NS NS
Asthma NS NS NS NS
Other comorbiditiesⴱ NS NS NS NS
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Any comorbidity NS NS NS NS
Tumor size (⬍ 4 cm or ⬎ 4 cm) .04 (⫺) NS NS NS
Histology NS NS NS NS
Copyright © 2024 American Society of Clinical Oncology. All rights reserved.

Tumor grade NS NS NS NS
Depth of invasion NS NS NS NS
Radiotherapy NS NS NS .03 (⫺)
Radical hysterectomy NS NS NS NS
Menopausal symptom score .004 (⫺) ⬍ .001 (⫺) NS NS

NOTE. P values are reported with either positive (⫹) or negative (⫺) association in parenthesis.
Abbreviations: SF-12 PCS, Short Form-12 Physical Component Score; SF-12 MCS, Short Form-12 Mental Component Score; BSI-18 GSI, Brief Symptom
Index-18 Global Severity Index; FSFI, Female Sexual Functioning Index; CAD, coronary artery disease.
ⴱ
Other comorbidities included hepatitis, migraines, and fibromyalgia.

(SF-12 PCS), mental health (SF-12 MCS), or emotional dis-
tress (BSI-18 GSI).
DISCUSSION
Our data showed that cervical cancer survivors treated with
surgery have far less sexual dysfunction than women treated
with radiotherapy at long-term follow-up (7 years). Fur-
thermore, women treated with radical hysterectomy resem-
ble their age- and race-matched peers who have never had a
cancer diagnosis or hysterectomy in physical, mental, emo-
tional, and sexual well-being.
Traditionally, oncologists have focused their efforts on
maximizing the overall survival of their patients. Although
many oncologists acknowledge that QOL after cancer ther-
apy is an important aspect of patient care, it is often not the
main consideration when recommending cancer treat-
ment. However, when competing treatment options result
in equivalent clinical outcomes, QOL considerations be-
come particularly important.
To our knowledge, this is the first study to measure not
just sexual functioning, but also emotional adjustment, rela-
tionship satisfaction, and menopause symptoms after surgery
or radiation treatment alone in patients with cervical cancer, as
well as in a group of women without a cancer diagnoses. The
consistently increased morbidity across all measures in irradi-
ated women is striking, and persists for sexual functioning
even after controlling for potentially confounding factors
such as educational level and tumor stage.
Although the desire for sexual intimacy was equal
among all groups, irradiated patients had significantly more
sexual dysfunction than women in the other two groups.
These findings agree with the previous prospective studies
comparing women treated with surgery alone or radiation
therapy alone.21-23 Jensen et al22 found women treated with
radiation therapy had more severe sexual dysfunction at
2-year follow-up, with 85% of women reporting no interest
in sex, 55% having dyspareunia, and 50% having vaginal
shortening. These problems were significant compared
with the women’s own premorbid sexual function and
when compared with age-matched controls.
The timing of follow-up is very important in these
patients since sexual and other morbidities improve during
the first year after radical hysterectomy,23 whereas the
chronic fibrotic changes in pelvic tissue after radiotherapy
create persistent, or even worsening vaginal atrophy at least
up to 2 years post-treatment.21,23 It is not surprising then to
find continued adverse sexual functioning in these women
who were irradiated 5 or more years ago. For these reasons,
we strongly recommend either the use of a vaginal dilator or

www.jco.org 7433
 Frumovitz et al
the engagement in sexual intercourse frequently after com-
pletion of radiotherapy for cervical cancer in an effort to
maintain the length, width, and elasticity of the vaginal
canal. Future research might follow these patients longitu-
dinally with pretreatment baseline sexual functioning data.
Patients who had undergone radical hysterectomy did
not differ in sexual functioning from age- and race-matched
peers. This finding is in accord with a previous study that
of early-stage cervical cancer patients treated with radical
surgery.24 In their second study, Jensen et al23 also found no
significant difference in overall sexual function between
women posthysterectomy and healthy controls. In contrast to
our results, women in the radical hysterectomy group were
almost three times more likely than controls to have difficulty
with vaginal lubrication. However, nearly one third of these
patients had undergone concurrent bilateral salpingo-
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oophorectomy, and no attempt was made to control for
menopausal status between treatment and control arms.
Copyright © 2024 American Society of Clinical Oncology. All rights reserved.
Bergmark et al25 have published the largest series on sex-
ual functioning in cervical cancer survivors. In their study, they
surveyed 256 Swedish cervical cancer survivors (4 to 6 years
after treatment) and compared them to controls matched for
age and geographic region. Their cancer arm was women with
local (stage IB) or locoregional (stage IIA) disease who had
been treated with a variety of modalities including radical
hysterectomy alone, radiation alone, and combination radio-
therapy and surgery. When comparing the entire cancer co-
hort to controls, they found no difference in sexual desire
or orgasm between the groups but found an increase age-
adjusted risk ratio for the cancer patients in regards to vaginal
lubrication, genital swelling/arousal, perceived vaginal length
and elasticity, dyspareunia, and coital bleeding. When they
performed a subanalysis grouped by treatment, they found no
difference in lubrication, genital swelling/arousal, vaginal elas-
ticity or length, or libido when comparing surgery patients
with irradiated patients to patients who had received multiple
modality therapy. They did, however, find that the surgery
only patients reported statistically significant differences in
vaginal lubrication, vaginal length, and vaginal elasticity when
compared with controls.
These findings contrast with the current study, which
showed significant differences on all subscales of the FSFI
(except arousal) for irradiated patients and no differences
between surgery only patients and controls. There are mul-
tiple possibilities for these discrepancies. First, Bergmark et
al utilized a survey created by them and not one that had been
subjected to tests of reliability and validity. Next, they did not
report or account for any ovarian procedures performed dur-
ing radical hysterectomy. Many of those women were made
menopausal with either surgery or radiation with little or no
accounting. In addition, their patient population, which in-
cluded women as old as 80 years and patients who had multiple
modality treatment differs greatly from ours. Finally, although
they reported hormonal status for both patients and controls,
7434
they made no attempt to control for it, or any other factor, in a
regression analysis, which likely introduced multiple con-
founders into the study.
The regression model we used performed the backwards
elimination in two steps. First, all of the demographic, medical
comorbidity, tumor, and treatment variables were added; the
menopausal symptom score was then inserted into the model.
Irradiated patients had statistically significant worse sexual
functioning, physical health, and emotional distress after the
first step, before the addition of the menopause symptom
score. After accounting for the menopause score, only sexual
functioning remained significantly worse for those women
who been irradiated. We believe that the irradiated patients
probably had worse physical health and possibly more psycho-
logic distress, but the menopausal symptom overall scores
masked the treatment effect in the statistical analysis be-
cause of the high one-to-one correlation between adverse
menopausal symptoms and the radiotherapy patients.
Therefore, the menopausal symptom score likely overshad-
owed the other relationships observed before its addition
into the multivariate model. When we compared patients
rendered menopausal by surgical oophorectomy with those
made climacteric by radiotherapy, menopausal symptom
scores were significantly worse for the irradiated women.
This was probably due to the fact that many of the symp-
toms surveyed by the instrument can be attributed to either
menopause or radiotherapy. This may explain why the two
groups with loss of ovarian function had similar rates of hot
flashes (symptoms unique to menopause) but differed signif-
icantly in their assessment of vaginal dryness and urinary
symptoms (likely a result of radiotherapy). In addition to caus-
ing ovarian failure, radiotherapy directly affects the vaginal
mucosa by decreasing blood flow to the vaginal walls and
causing pelvic fibrosis. For these reasons, even topical estrogen
cream is less well absorbed and less effective in reversing meno-
pausal changes in the vagina after radiotherapy.26
Severity of menopausal symptom scores correlated with
poor QOL on all four modeled measures. Not surprisingly,
patients who reported increased menopausal symptoms also
had poor sexual functioning. Abrupt and premature meno-
pause resulting from cancer treatment has also been observed
to account for most of the sexual dysfunction women experi-
ence after breast cancer.27 In published studies, effects of
menopause on physical and emotional QOL have not been
clearly established.28-30 The association seen in our study may
be due to the sudden and severe nature of menopause onset
resulting from pelvic irradiation.
We did not specifically ask participants whether or
not they were taking hormone replacement at the time of
the survey. Our study was conducted in the wake of the
publication of the Women’s Health Initiative data and
the ensuing publicity created in both the medical and lay
media. Many of the women who reported menopausal
symptoms may have recently discontinued their hormone
JOURNAL OF CLINICAL ONCOLOGY
 QOL in Cervical Cancer

replacement therapy and therefore may have been experi-
encing more climacteric dysfunction. Since more irradiated
patients were rendered menopausal than surgery patients,
the timing of the survey may have falsely elevated their
menopausal symptom scores skewing some of the results.
Other interesting variables affected QOL in our study
population. For example, smoking was shown to have a nega-
tive correlation with mental and emotional well-being. Other
investigators have also found higher rates of depression31 and
suicide32 among smokers. It is possible, however, that women
who are aware of the role of smoking in cervical cancer, but
who continue to smoke after their treatment, may have a
particularly negative perception of their health status.
Although these data support anecdotal experience
associated with the two treatment modalities, we are not
suggesting that all patients with cervical cancer who are
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study were diagnosed at least 5 years ago when chemoradio-
therapy was administered only on experimental protocols.
However, it is unlikely that concurrent chemotherapy would
improve the ultimate QOL in patients undergoing radiother-
apy for cervical cancer, given reports of increased acute com-
plications and lack of reduction in delayed complications.36
As with all studies based on surveys, response bias may
affect results. Selection bias occurs if patients and control
group participants who take part in the study have a better
quality of life than those who are unreachable or refuse to
participate. Also, not all patients interviewed have been
followed at M.D. Anderson since the completion of their
treatment. The low socioeconomic status of this population
as well as the long interval from treatment to contact for this
study made locating and recruiting these patients difficult.
A standard recruitment goal in retrospective survey studies

surgical candidates should be treated with radical hysterec- is a response rate of at least 60%.37 For both treatment
tomy. Careful patient selection must be made in an effort to groups surveyed, the response rate was 54%, so the results
Copyright © 2024 American Society of Clinical Oncology. All rights reserved.

avoid the need for adjuvant radiotherapy after radical sur-
gery. Even some patients with clinical stage IB1 cancers will
need postoperative radiotherapy,33 and this risk increases
with tumor size and clinical stage.34 Complication rates for
patients requiring both treatment modalities are higher
than for those having had either treatment alone.33,35
While the few baseline differences that existed between
the treatment groups and the controls were accounted for in
the multivariate models, other factors biasing the results
cannot be excluded. For example, although all tumors were
limited to the cervix and smaller than 6 cm in diameter,
surgical patients all had earlier stage tumors than did those
treated with radiation. However, we believe that these le-
sions behave in a similar manner clinically and therefore
this difference in substage (all patients had stage I [local-
ized] disease) should not affect these outcome measures.
Furthermore, a statistically significant difference in tumor
histologies existed between the two treatment arms. The
radical hysterectomy group had larger numbers of adeno-
carcinoma and adenosquamous carcinoma. Grade for
grade, these histologies tend to be more aggressive than
squamous lesions. Patients who were not cured of these
more malignant lesions by primary treatment would likely
have been excluded from this study because of persistent or
recurrent disease or additional surgical or radiotherapies
after initial treatment.
The radiation group was treated without concurrent che-
motherapy, which is now the standard of care. Patients in this
may not be generalizable to the general population of cer-
vical cancer survivors. Finally, since data were collected
retrospectively, we do not know if a quality of life difference
may have existed in the treatment groups before therapy.
Our data suggest that cervical cancer survivors treated
primarily with radical hysterectomy and lymph node dissec-
tion have less sexual dysfunction than patients treated with
radiotherapy. In addition, patients treated surgically seemingly
have no difference in QOL, psychosocial stress, or sexual func-
tioning than age- and race-matched control group partici-
pants who neither had cancer nor a hysterectomy. At present
we do not know how current protocols that combine surgery
with adjuvant radiotherapy affect QOL, so these results should
be used judiciously in recommending surgery over radiation
for bulky or advanced-stage disease. By incorporating empiri-
cal data regarding long-term quality-of-life outcomes into the
clinical decision-making process for treating early-stage cervix
cancer, our data may assist both the patient and her physician
in selecting the most appropriate treatment.
■ ■ ■
Acknowledgment
We thank Robert Coleman for his contribution to the
editing of this manuscript.
Authors’ Disclosures of Potential
Conflicts of Interest
The authors indicated no potential conflicts of interest.

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